Extended-release topiramate capsules

Abstract

An extended-release topiramate capsule that includes a capsule shell containing a single population of coated particles; wherein each coated particle includes a core and a coating thereon; wherein each particle core includes a homogeneous mixture comprising topiramate throughout its core; and wherein the coating includes one or more release controlling agent(s).

What is claimed is: 
     
       1. A container comprising an extended-release topiramate capsule and desiccant, wherein the extended-release topiramate capsule comprises:
 a capsule shell comprising a single population of coated particles;
 wherein each coated particle comprises a core and a coating thereon; 
 wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:
 topiramate; 
 one or more filler(s); and 
 one or more binder(s); 
 
 
 wherein the coating comprises:
 one or more release controlling agent(s); 
 one or more pore former(s); and 
 one or more plasticizer(s); 
 
 wherein the components in the particle core and coating are present in amounts that provide extended release of topiramate; and 
 wherein, when a single dose is given to a healthy human subject, an AUC 0-inf  of 170 to 210 h·μg/mL within a 95% confidence interval, and a C max  of 2 to 4 μg/mL within a 95% confidence interval are achieved in the subject's plasma. 
 
     
     
       2. The container of  claim 1  wherein the ratio of weight of desiccant to weight of filled capsules is at least 0.01. 
     
     
       3. The container of  claim 1  wherein the ratio of weight of desiccant to weight of filled capsules is up to 0.9. 
     
     
       4. The container of  claim 1  wherein the desiccant is selected from silica gel, bentonite clay, molecular sieve, and combinations thereof. 
     
     
       5. A container comprising an extended-release topiramate capsule and desiccant, wherein the extended-release topiramate capsule comprises:
 a capsule shell comprising a single population of coated particles;
 wherein each coated particle comprises a core and a coating thereon; 
 wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:
 40 wt-% to 50 wt-% of topiramate, based on the total weight of an uncoated particle core; 
 45 wt-% to 55 wt-% of one or more filler(s), based on the total weight of an uncoated particle core; and 
 3 wt-% to 7 wt-% of one or more binder(s), based on the total weight of an uncoated particle core; 
 
 
 wherein the coating comprises:
 55 wt-% to 65 wt-% of one or more release control agent(s), based on the total weight of the coating; 
 20 wt-% to 25 wt-% of one or more pore former(s), based on the total weight of the coating; and 
 10 wt-% to 20 wt-% of one or more plasticizer(s), based on the total weight of the coating; 
 
 wherein the particles are coated in an amount sufficient to provide a weight gain of 8% to 14%. 
 
     
     
       6. The container of  claim 5  wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:
 40 wt-% to 50 wt-% of topiramate, based on the total weight of an uncoated particle core; 
 45 wt-% to 55 wt-% of one or more filler(s), based on the total weight of an uncoated particle core; wherein the one or more filler(s) is selected from the group of microcrystalline cellulose, dibasic calcium phosphate, lactose, tribasic calcium phosphate, mannitol, and combinations thereof; and 
 3 wt-% to 7 wt-% of one or more binder(s), based on the total weight of an uncoated particle core; wherein the one or more binder(s) is selected from the group of hydroxypropyl methylcellulose, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, hydroxypropyl cellulose, hydroxyethylcellulose, polyvinyl pyrrolidine, starch, natural gum, and combinations thereof; 
 wherein the coating comprises:
 55 wt-% to 65 wt-% of one or more release control agent(s), based on the total weight of the coating; wherein the one or more release controlling agent(s) is selected from the group of ethylcellulose, polyvinyl acetate, polyacrylate and polymethacrylate, copolymers thereof, and combinations thereof; 
 20 wt-% to 25 wt-% of one or more pore former(s), based on the total weight of the coating; wherein the one or more pore former(s) is selected from the group of hypromellose, hydroxypropyl cellulose, methylcellulose, hydroxyethylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, polyethylene glycol, guar gum, xanthan gum, sodium alginate, polyvinylpyrrolidone, crospovidone, sodium starch glycolate, croscarmellose sodium, starch, mannitol, glucose, sucrose, fructose, mannose, galactose, sorbitol, dextran, sodium chloride, potassium chloride, calcium chloride, and combinations thereof; and 
 10 wt-% to 20 wt-% of one or more plasticizer(s), based on the total weight of the coating; wherein the one or more plasticizer(s) is selected from the group of diethyl phthalate, triethyl citrate, dibutyl sebacate, polyethylene glycol, triacetin, tributyl citrate, glycerol, propylene glycol, and combinations thereof; 
 
 wherein the particles are coated in an amount sufficient to provide a weight gain of 8% to 14%. 
 
     
     
       7. The container of  claim 6  wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:
 40-50 wt-% of topiramate, based on the total weight of an uncoated particle core; 
 45-55 wt-% of microcrystalline cellulose, based on the total weight of an uncoated particle core; and 
 3-7 wt-% of hydroxypropyl methylcellulose, based on the total weight of an uncoated particle core; 
 wherein the coating comprises:
 55-65 wt-% of ethylcellulose, based on the total weight of the coating; 
 20-25 wt-% of hydroxypropyl methylcellulose, based on the total weight of the coating; and 
 10-20 wt-% of diethyl phthalate, based on the total weight of the coating; 
 
 wherein the particles are coated in an amount sufficient to provide a weight gain of 8% to 14%. 
 
     
     
       8. The container of  claim 7  wherein each particle core comprises a homogeneous mixture throughout its core, the mixture comprising:
 44-46 wt-% of topiramate, based on the total weight of an uncoated particle core; 
 48-52 wt-% of microcrystalline cellulose, based on the total weight of an uncoated particle core; and 
 4-6 wt-% of hydroxypropyl methylcellulose, based on the total weight of an uncoated particle core; 
 wherein the coating comprises:
 60-62 wt-% of ethylcellulose, based on the total weight of the coating; 
 22-24 wt-% of hydroxypropyl methylcellulose, based on the total weight of the coating; and 
 15-18 wt-% of diethyl phthalate, based on the total weight of the coating; 
 
 wherein the particles are coated in an amount sufficient to provide a weight gain of 10-12%. 
 
     
     
       9. The container of  claim 5  wherein the ratio of weight of desiccant to weight of filled capsules is at least 0.01. 
     
     
       10. The container of  claim 5  wherein the ratio of weight of desiccant to weight of filled capsules is up to 0.9. 
     
     
       11. The container of  claim 5  wherein the desiccant is selected from silica gel, bentonite clay, molecular sieve, and combinations thereof.